We are using topical nitrosourea compounds in the treatment of mycosis fungoides. To date solutions of 1-(2-chloroethyl) -1- nitrosourea (NSC 47547), methylnitrosourea (NSC 23909), 1,3-bis(2- chloroethyl)-1-nitrosourea (BCNU), and 1-(2-chloroethyl)-3-cyclohexyl-1- nitrosourea (CCNU) have been used in some twenty patients. Most of the patients in the past year have been treated with aqueous and alcoholic solutions of BCNU (1-3 mg/ml) and CCNU (2-4 mg/ml). As a rule, plaques will clear after 7-14 days of daily applications. No bone marrow or other toxicity has been seen. There is no cross sensitivity to nitrogen mustard, so that the patients allergic to nitrogen mustard can be treated with nitrosourea compounds. Attempts to demonstrate intact BCNU in the plasm or urine after topical application have been unsuccessful. Preliminary findings indicate that nitrosourea compounds are less carcinogenic than methylcholanthrene when applied topically to mice. Both BCNU and nitrogen mustard have a direct stimulatory effect on melanocytes when applied to hairless mice but they produce different morphologic changes in such cells. We propose to study the percutaneous penetration of C14-BCNU in humans.